The mechanisms regulating meiotic initiation in mammals are enigmatic. STRA8, which is expressed in response to retinoic acid, is thought to be a key factor promoting meiotic initiation. However, the specific role of STRA8 in meiotic initiation has remained elusive. Previously, we identified MEIOSIN as a germ cell-specific factor that associates with STRA8 (Ishiguro et al. Dev Cell 2020). MEIOSIN, in collaboration with STRA8, drives meiotic gene activation, and plays an essential role in the switching from mitosis to meiosis.
Here we show that STRA8 binds to RB families, independently of MEIOSIN. To study the physiological relevance of STRA8-RB interaction, we generated mutant mice that express STRA8 lacking RB-binding site (Stra8ΔRB), in which STRA8 cannot bind to RB but preserves intact interaction with MEIOSIN. Notably, our genetic study combined with scRNA-seq analysis demonstrated that in Stra8ΔRB female germ cells, progression into G1/S transition was compromised and meiotic entry was concomitantly delayed. This suggests that meiotic initiation is coordinated to coincide with S phase under STRA8-RB interaction in female germ cells. Intriguingly, although Stra8ΔRB oocytes apparently progressed through meiotic prophase, they failed to undergo dictyate arrest, a status of prolonged G2 arrest, resulting in premature loss of oocyte pool. Our study highlights the previously unforeseen implication that oocyte intrinsic program of long-term G2 arrest, is genetically controlled under STRA8-RB interaction.